Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: The ENTRANCE study

• Published in: Journal of Crohn's and colitis 2013-09, Vol.7 (8), p.636-643
• Main Authors: Herrlinger, K.R., Diculescu, M., Fellermann, K., Hartmann, H., Howaldt, S., Nikolov, R., Petrov, A., Reindl, W., Otte, J.M., Stoynov, S., Strauch, U., Sturm, A., Voiosu, R., Ammendola, A., Dietrich, B., Hentsch, B., Stange, E.F.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anti-Inflammatory Agents - therapeutic use; Azathioprine - therapeutic use; Biphenyl Compounds - adverse effects; Biphenyl Compounds - therapeutic use; Blood Sedimentation; C-Reactive Protein - metabolism; Clinical trial; Colitis, Ulcerative - blood; Colitis, Ulcerative - drug therapy; Crohn Disease - blood; Crohn Disease - drug therapy; Crohn's disease; Dicarboxylic Acids - adverse effects; Dicarboxylic Acids - therapeutic use; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - therapeutic use; Feces - chemistry; Female; Humans; IBD; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Immunosuppressive Agents - therapeutic use; Intention to Treat Analysis; Leukocyte L1 Antigen Complex - analysis; Male; Methotrexate - therapeutic use; Middle Aged; Oxidoreductases Acting on CH-CH Group Donors - antagonists & inhibitors; Prednisolone - therapeutic use; Remission Induction; Severity of Illness Index; Ulcerative colitis; Vidofludimus; Young Adult
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1016/j.crohns.2012.09.016

Vidofludimus (SC12267) is a novel oral immunomodulator inhibiting dihydroorotate dehydrogenase (DHODH) and the expression of proinflammatory cytokines including interleukin-17 (IL17A and IL17F) and interferon-gamma. The objective of the study was to explore the efficacy, safety and tolerability of vidofludimus in steroid-dependent inflammatory bowel disease (IBD). The open label uncontrolled ENTRANCE study (ClinicalTrials.gov NCT00820365) has been conducted at 13 study centers in Germany, Bulgaria and Romania. Thirty-four steroid-dependent patients with a confirmed diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were treated with a once daily 35mg oral dose of vidofludimus over 12weeks. Steroids were tapered during the first 8weeks followed by a steroid-free treatment period of 4weeks. Complete response was defined as steroid-free clinical remission at week 12; partial response was defined as being in remission at steroid dose equal or lower than the individual patient's threshold dose for relapse. Of the thirty-four patients enrolled in this trial 26 were evaluable for primary efficacy assessment. After completion of the 12weeks treatment phase 8 out of 14 (57.1%) patients with CD and 6 out of 12 (50.0%) patients with UC were in steroid-free remission (complete responders). Another 4 (28.6%) patients in CD and 5 (41.7%) patients in UC were partial responders. Vidofludimus was well tolerated, no drug-related serious adverse events were observed. This trial provides first evidence of clinical efficacy of vidofludimus in IBD. Although the safety and tolerability profile seems favorable, long-term controlled studies are needed to further investigate its potential as novel IBD therapy.